A Novel Loss-of-Function Mutation in the NPRL3 Gene Identified in Chinese Familial Focal Epilepsy with Variable Foci
Familial focal epilepsy with variable foci is an autosomal dominant disorder characterized by partial epilepsy with variable foci. In this study, we report a six-generation with segregation of the mutation present in four generations Chinese family presenting with focal epilepsy with variable foci....
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Frontiers Media S.A.
2021
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oai:doaj.org-article:567b048d43104f6ea99365744cb2a7d62021-11-12T06:34:43ZA Novel Loss-of-Function Mutation in the NPRL3 Gene Identified in Chinese Familial Focal Epilepsy with Variable Foci1664-802110.3389/fgene.2021.766354https://doaj.org/article/567b048d43104f6ea99365744cb2a7d62021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.766354/fullhttps://doaj.org/toc/1664-8021Familial focal epilepsy with variable foci is an autosomal dominant disorder characterized by partial epilepsy with variable foci. In this study, we report a six-generation with segregation of the mutation present in four generations Chinese family presenting with focal epilepsy with variable foci. Whole exome sequencing confirms a novel pathogenic mutation in the NPRL3 gene (c316C>T; p. Q106*). PCR, Western blotting, and immunohistochemistry were conducted to analyze the gene transcription, protein expression, and subcellular localization of NPRL3 and related signaling molecules in peripheral blood cells from family members. As compared with healthy family members, both mRNA level and protein expression of NPRL3 are decreased in peripheral blood cells of the mutation carrier. In addition, the expression of downstream molecular Phospho-p70 S6 kinase (P-s6k) are increased consequently. Our findings expand the genotypic and phenotypic spectrum of the NPRL3-associated epilepsy and reveal the mechanisms of mTOR pathway signaling and GATOR1 pathogenesis in focal epilepsies, providing exciting potential for future diagnostic and therapeutic interventions. However, further in vitro and animal experiments are still needed to evaluate the role of NPRL3 loss-of-function mutation in epileptogensis.Youzhi LiXu ZhaoShanshan WangKe XuXin ZhaoShanshan HuangSuiqiang ZhuFrontiers Media S.A.articleGATOR1Nprl3mTOR signaling pathwaywhole-exome sequencing (WES)familial focal epilepsy with variable fociGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021) |
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GATOR1 Nprl3 mTOR signaling pathway whole-exome sequencing (WES) familial focal epilepsy with variable foci Genetics QH426-470 |
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GATOR1 Nprl3 mTOR signaling pathway whole-exome sequencing (WES) familial focal epilepsy with variable foci Genetics QH426-470 Youzhi Li Xu Zhao Shanshan Wang Ke Xu Xin Zhao Shanshan Huang Suiqiang Zhu A Novel Loss-of-Function Mutation in the NPRL3 Gene Identified in Chinese Familial Focal Epilepsy with Variable Foci |
| description |
Familial focal epilepsy with variable foci is an autosomal dominant disorder characterized by partial epilepsy with variable foci. In this study, we report a six-generation with segregation of the mutation present in four generations Chinese family presenting with focal epilepsy with variable foci. Whole exome sequencing confirms a novel pathogenic mutation in the NPRL3 gene (c316C>T; p. Q106*). PCR, Western blotting, and immunohistochemistry were conducted to analyze the gene transcription, protein expression, and subcellular localization of NPRL3 and related signaling molecules in peripheral blood cells from family members. As compared with healthy family members, both mRNA level and protein expression of NPRL3 are decreased in peripheral blood cells of the mutation carrier. In addition, the expression of downstream molecular Phospho-p70 S6 kinase (P-s6k) are increased consequently. Our findings expand the genotypic and phenotypic spectrum of the NPRL3-associated epilepsy and reveal the mechanisms of mTOR pathway signaling and GATOR1 pathogenesis in focal epilepsies, providing exciting potential for future diagnostic and therapeutic interventions. However, further in vitro and animal experiments are still needed to evaluate the role of NPRL3 loss-of-function mutation in epileptogensis. |
| format |
article |
| author |
Youzhi Li Xu Zhao Shanshan Wang Ke Xu Xin Zhao Shanshan Huang Suiqiang Zhu |
| author_facet |
Youzhi Li Xu Zhao Shanshan Wang Ke Xu Xin Zhao Shanshan Huang Suiqiang Zhu |
| author_sort |
Youzhi Li |
| title |
A Novel Loss-of-Function Mutation in the NPRL3 Gene Identified in Chinese Familial Focal Epilepsy with Variable Foci |
| title_short |
A Novel Loss-of-Function Mutation in the NPRL3 Gene Identified in Chinese Familial Focal Epilepsy with Variable Foci |
| title_full |
A Novel Loss-of-Function Mutation in the NPRL3 Gene Identified in Chinese Familial Focal Epilepsy with Variable Foci |
| title_fullStr |
A Novel Loss-of-Function Mutation in the NPRL3 Gene Identified in Chinese Familial Focal Epilepsy with Variable Foci |
| title_full_unstemmed |
A Novel Loss-of-Function Mutation in the NPRL3 Gene Identified in Chinese Familial Focal Epilepsy with Variable Foci |
| title_sort |
novel loss-of-function mutation in the nprl3 gene identified in chinese familial focal epilepsy with variable foci |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/567b048d43104f6ea99365744cb2a7d6 |
| work_keys_str_mv |
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